The role of arachidonate lipoxygenase and fatty acids during irreversible blood platelet aggregation in vitro.
Arachidonic acid is converted by blood platelets into thromboxane A2 (TXA2) and 12-hydroxyeicosatetraenoic acid (12-OH-C20:4). TXA2 causes platelet aggregation, but the physiological role of 12-OH-C20:4 on blood platelets is not known. The formation of 12-OH-C20:4 by washed platelets can be inhibited by eicosatetraynoic acid at a concentration of 0.7 mumol/l; TXA2-formation is not yet influenced at this low inhibitor concentration. Under these conditions, the irreversible 1-14C arachidonic acid-induced blood platelet aggregation is converted into a reversible type of aggregation. Similar results are obtained by addition of any long-chain fatty acid (20-30 mumol/l), including 12-OH-C20:4 and arachidonic acid, as well as by addition of sulfhydryl reagents. However, in these experiments no inhibition of the arachidonic acid conversion is observed. The results can be explained by a "sticking together" of the blood platelets caused by 12-OH-C20:4 generation. This effect is based on the same principle as that of the chemotactic effect of 12-OH-C20:4 on leucocytes as described by Turner et al. (Nature 257; 680-681, 1975). The explanation is supported by experiments with platelets obtained after ingestion of aspirin. ADP-induced reversible aggregation of three platelets becomes irreversible after addition of arachidonic acid. Irreversible platelet aggregation occurs only during endogenous 12-OH-C20:4 generation in consequence of a "sticking-together" process. This process coincides with a stimulation of the platelet guanylate cyclase.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D001091:Arachidonate Lipoxygenases; D001095:Arachidonic Acids / Q000097:blood; D005227:Fatty Acids / Q000097:blood*; D006801:Humans; D008084:Lipoxygenase / Q000097:blood*; D010974:Platelet Aggregation
D001095:Arachidonic Acids; D005227:Fatty Acids; D015117:5,8,11,14-Eicosatetraynoic Acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001091:Arachidonate Lipoxygenases; D008084:Lipoxygenase